Reactive Oxygen Species Mediate the Suppression of Arterial Smooth Muscle T-type Ca2+ Channels by Angiotensin II

Abstract Vascular T-type Ca2+ channels (CaV3.1 and CaV3.2) play a key role in arterial tone development. This study investigated whether this conductance is a regulatory target of angiotensin II (Ang II), a vasoactive peptide that circulates and which is locally produced within the arterial wall. Pa...

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Autores principales:	Ahmed M. Hashad, Maria Sancho, Suzanne E. Brett, Donald G. Welsh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/303109c026ad425cb293f8870ac61ba9
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spelling	oai:doaj.org-article:303109c026ad425cb293f8870ac61ba92021-12-02T12:32:35ZReactive Oxygen Species Mediate the Suppression of Arterial Smooth Muscle T-type Ca2+ Channels by Angiotensin II10.1038/s41598-018-21899-52045-2322https://doaj.org/article/303109c026ad425cb293f8870ac61ba92018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-21899-5https://doaj.org/toc/2045-2322Abstract Vascular T-type Ca2+ channels (CaV3.1 and CaV3.2) play a key role in arterial tone development. This study investigated whether this conductance is a regulatory target of angiotensin II (Ang II), a vasoactive peptide that circulates and which is locally produced within the arterial wall. Patch clamp electrophysiology performed on rat cerebral arterial smooth muscle cells reveals that Ang II (100 nM) inhibited T-type currents through AT1 receptor activation. Blocking protein kinase C failed to eliminate channel suppression, a finding consistent with unique signaling proteins enabling this response. In this regard, inhibiting NADPH oxidase (Nox) with apocynin or ML171 (Nox1 selective) abolished channel suppression highlighting a role for reactive oxygen species (ROS). In the presence of Ni2+ (50 µM), Ang II failed to modulate the residual T-type current, an observation consistent with this peptide targeting CaV3.2. Selective channel suppression by Ang II impaired the ability of CaV3.2 to alter spontaneous transient outward currents or vessel diameter. Proximity ligation assay confirmed Nox1 colocalization with CaV3.2. In closing, Ang II targets CaV3.2 channels via a signaling pathway involving Nox1 and the generation of ROS. This unique regulatory mechanism alters BKCa mediated feedback giving rise to a “constrictive” phenotype often observed with cerebrovascular disease.Ahmed M. HashadMaria SanchoSuzanne E. BrettDonald G. WelshNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ahmed M. Hashad Maria Sancho Suzanne E. Brett Donald G. Welsh Reactive Oxygen Species Mediate the Suppression of Arterial Smooth Muscle T-type Ca2+ Channels by Angiotensin II
description	Abstract Vascular T-type Ca2+ channels (CaV3.1 and CaV3.2) play a key role in arterial tone development. This study investigated whether this conductance is a regulatory target of angiotensin II (Ang II), a vasoactive peptide that circulates and which is locally produced within the arterial wall. Patch clamp electrophysiology performed on rat cerebral arterial smooth muscle cells reveals that Ang II (100 nM) inhibited T-type currents through AT1 receptor activation. Blocking protein kinase C failed to eliminate channel suppression, a finding consistent with unique signaling proteins enabling this response. In this regard, inhibiting NADPH oxidase (Nox) with apocynin or ML171 (Nox1 selective) abolished channel suppression highlighting a role for reactive oxygen species (ROS). In the presence of Ni2+ (50 µM), Ang II failed to modulate the residual T-type current, an observation consistent with this peptide targeting CaV3.2. Selective channel suppression by Ang II impaired the ability of CaV3.2 to alter spontaneous transient outward currents or vessel diameter. Proximity ligation assay confirmed Nox1 colocalization with CaV3.2. In closing, Ang II targets CaV3.2 channels via a signaling pathway involving Nox1 and the generation of ROS. This unique regulatory mechanism alters BKCa mediated feedback giving rise to a “constrictive” phenotype often observed with cerebrovascular disease.
format	article
author	Ahmed M. Hashad Maria Sancho Suzanne E. Brett Donald G. Welsh
author_facet	Ahmed M. Hashad Maria Sancho Suzanne E. Brett Donald G. Welsh
author_sort	Ahmed M. Hashad
title	Reactive Oxygen Species Mediate the Suppression of Arterial Smooth Muscle T-type Ca2+ Channels by Angiotensin II
title_short	Reactive Oxygen Species Mediate the Suppression of Arterial Smooth Muscle T-type Ca2+ Channels by Angiotensin II
title_full	Reactive Oxygen Species Mediate the Suppression of Arterial Smooth Muscle T-type Ca2+ Channels by Angiotensin II
title_fullStr	Reactive Oxygen Species Mediate the Suppression of Arterial Smooth Muscle T-type Ca2+ Channels by Angiotensin II
title_full_unstemmed	Reactive Oxygen Species Mediate the Suppression of Arterial Smooth Muscle T-type Ca2+ Channels by Angiotensin II
title_sort	reactive oxygen species mediate the suppression of arterial smooth muscle t-type ca2+ channels by angiotensin ii
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/303109c026ad425cb293f8870ac61ba9
work_keys_str_mv	AT ahmedmhashad reactiveoxygenspeciesmediatethesuppressionofarterialsmoothmusclettypeca2channelsbyangiotensinii AT mariasancho reactiveoxygenspeciesmediatethesuppressionofarterialsmoothmusclettypeca2channelsbyangiotensinii AT suzanneebrett reactiveoxygenspeciesmediatethesuppressionofarterialsmoothmusclettypeca2channelsbyangiotensinii AT donaldgwelsh reactiveoxygenspeciesmediatethesuppressionofarterialsmoothmusclettypeca2channelsbyangiotensinii
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Reactive Oxygen Species Mediate the Suppression of Arterial Smooth Muscle T-type Ca2+ Channels by Angiotensin II

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